Zinc-finger protein 545 is inactivated due to promoter methylation and functions as a tumor suppressor through the Wnt/β-catenin, PI3K/AKT and MAPK/ERK signaling pathways in colorectal cancer

Xiang,Shili; Xiang,Tingxiu; Xiao,Qian; Li,Yunhai; Shao,Bianfei; Luo,Tao

doi:10.3892/ijo.2017.4064

Zinc-finger protein 545 is inactivated due to promoter methylation and functions as a tumor suppressor through the Wnt/β-catenin, PI3K/AKT and MAPK/ERK signaling pathways in colorectal cancer

Authors:
- Shili Xiang
- Tingxiu Xiang
- Qian Xiao
- Yunhai Li
- Bianfei Shao
- Tao Luo
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Affiliations: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Breast and Thyroid, The Hospital of Chongqing Traditional Chinese Medicine, Chongqing 400011, P.R. China
Published online on: July 4, 2017 https://doi.org/10.3892/ijo.2017.4064
Pages: 801-811
Copyright: © Xiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The transcription factor, zinc-finger protein 545 (ZNF545), that belongs to the Kruppel-associated box zinc-finger protein (KRAB-ZFP) family, acts as a tumor suppressor and is inactivated by promoter methylation in cancers such as nasopharyngeal carcinoma, breast cancer, and gastric cancer, but its role in colorectal cancer (CRC) is unknown. The purpose of this study was to characterize the ZNF545 expression, methylation status, biological function, and related molecular mechanisms in CRC. The results showed that ZNF545 was expressed in adult normal colorectal tissues, but downregulated or silenced in CRC cell lines, and this mechanism was reversed by demethylation treatment with 5-aza-2'-deoxycytidine and trichostatin A. The results also showed that the expression of ZNF545 in primary CRC tissues was significantly downregulated compared to adjacent tissues (p<0.05). Overexpression of ZNF545 caused CRC cell cycle arrest and apoptosis, suppressed cell proliferation, and suppressed colony formation and migration in vitro, showing that ZNF545 can function as a tumor suppressor. This function was also shown in nude mice. Furthermore, Wnt/β‑catenin, phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), and mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways participated in the regulation of ZNF545 in CRC cells. Together, the results suggested that ZNF545 functions as a tumor suppressor in CRC and is frequently inactivated by promoter methylation.

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